First Aldol Cross-Linked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Hydrogel with Tissue Adhesive Properties

Daniel Bermejo-Velasco, Sandeep Kadekar, Marcus Vinicius Tavares Da Costa, Oommen P. Oommen, Kristofer Gamstedt, Jöns Hilborn, Oommen P. Varghese

Research output: Contribution to journalArticleScientificpeer-review

8 Citations (Scopus)


Currently, there are limited approaches to tailor 3D scaffolds cross-linked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-cross-linking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely, an enolizable HA-aldehyde (HA-Eal) and a non-enolizable HA-aldehyde (HA-Nal). Hydrogels formed using HA-Eal demonstrate inferior cross-linking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-Eal and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of cross-linking at different pH values is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Mc). The novel HA cross-aldol hydrogel demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase-mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product rendered the tissue-adhesive properties by bonding two bone tissues. The aldehyde functionality also facilitated facile post-synthetic modifications with nucleophilic reagents. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3-6 days of study.

Original languageEnglish
JournalACS Applied Materials and Interfaces
Publication statusE-pub ahead of print - 2019
Publication typeA1 Journal article-refereed


  • aldol chemistry
  • biomaterial
  • hyaluronic acid
  • hydrogel
  • tissue adhesive

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Materials Science(all)


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